Expression Levels of Enzymes Metabolizing an Anticancer Drug Ellipticine Determined by Electromigration Assays Influence its Cytotoxicity to Cancer Cells - A Comparative Study

摘要

The antineoplastic alkaloid ellipticine is a prodrug, of which the pharmacological efficiency isdependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to 12-hydroxy- and13-hydroxyellipticine, which are both the metabolites forming DNA adducts in target tissues. Usingthe method of Western blotting, the expression of CYP1A1, 1B1, 3A4, lactoperoxidase, thyroidperoxidase, cyclooxygenase-1 and cytochrome b5, the enzymes that catalyze and/or influenceellipticine metabolism, was investigated in several cancer cells sensitive to ellipticine (HL-60promyelocytic leukemia and T-cell leukemia CCRF-CEM cells, glioblastoma U87MG cells, thyroidcancer BHT-101, B-CPAP and 8505-C cells, neuroblastoma UKF-NB-3 and UKF-NB-4 cell lines andbreast adenocarcinoma MCF-7 cells). The findings summarized from several former studies reviewedin this study, together with new results indicate that, depending on individual cells, cytotoxicity ofellipticine, which is mediated by formation of covalent DNA adducts to these cancer cells, isinfluenced by expression levels of these CYP and peroxidase enzymes in the tested cancer cells.Furthermore, a potency of ellipticine to induce the enzymes dictating activation of ellipticine to formDNA adducts in studied cancer cells determines an increase in cytotoxicity of ellipticine to these tumorcells.